Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis.
BACKGROUND
Recently we observed that ursodeoxycholic acid (UDCA) ameliorates an experimental small intestinal inflammation induced by indomethacin in the rat. In this study, we have tested whether ursodeoxycholic acid also reduces mucosal damage in the bile-independent trinitrobenzene sulphonic acid (TNB) model of experimental colitis.


METHODS
Intestinal inflammation (colitis) was induced in male Sprague-Dawley rats (250-300 g) by intracolonic administration of TNB (30 mg in 50% ethanol). Rats were treated with UDCA (10 mg/kg) either for 3 days starting with the administration of TNB for an acute inflammation (n = 11) or for 8 days starting one day after induction of colitis related to a more acute/chronic inflammation (n = 11). Rats were sacrificed at day 3 or day 9, respectively. Healing of induced colitis was assessed by macroscopic and blinded microscopic analysis as well as by measurement of bowel wet weight, daily body weight, and myeloperoxidase activity. All examinations were separately performed in three colon segments (S1 3-5 cm, S2 5.5-8 cm and S3 8.5-11 cm from anus).


RESULTS
UDCA treatment significantly reduced macroscopically and microscopically detectable injury in acute inflammation in segments 1 and 2. The colitis-rats with acute/chronic inflammation had less marked mucosal damage. Nevertheless, UDCA treatment led to a significant decrease of visible injury parameters which was seen exclusively at the area of maximal ulceration (S2). Furthermore, a significant increase in body weight of UDCA-treated TNB rats compared to controls from day 5 on was found.


CONCLUSIONS
Ursodeoxycholic acid attenuates the severity of acute inflammation and inhibits the development of acute/chronic inflammation predominantly around the area of maximal ulceration in TNB-induced colitis. In addition to our previous studies and results in indomethacin induced enteritis, these data may provide a rationale for studying how UDCA modulates functions of immune cells in the colonic mucosa.
Kullmann
F
F
Department of Internal Medicine, University of Regensburg, Germany.
Arndt
H
H
Gross
V
V
Rüschoff
J
J
Schölmerich
J
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D014580:Ursodeoxycholic Acid; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase